The ocean represents an important source of second metabolites, with its indeterminate number of organisms, such as the bryozoa, mollusca and porifera species. The potential of discovering natural products present in marine sponges and the bacteria, fungi and protists, associated with them, has been explored only to a slight extent. The diversity and structural properties of these natural products can be simulated only at great expense, with classical synthetic methods. An above average number of these natural products have biological properties which are worth following up. Accordingly, they are of interest as potential active ingredients or as novel guiding structures for the development of pharmaceuticals.
Marine sponges require an efficient defense mechanism because of their habitat. It is therefore very likely that highly biologically active compounds can be isolated from these sponges, albeit in very low concentrations. Halichondrin, spongistatin 1, ocadaic acid as well as swinholide A are mentioned as examples of such compounds, which have been successfully isolated from sponges.
The multitude of substances present in extracts of the aforementioned marine organisms require methods for rapidly and intensively differentiating between compounds already known and those which are new. In particular, the “LC triad” is mentioned here which represents a coupling of high performance liquid chromatography (HPLC) with nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS) and circular dichroism (CD) spectroscopy (G. Bringmann et al., ANAL. CHEM. 1998, 70, 2805-2811 and G. Bringmann et al., ANAL. CHEM., 1999, 71, 2678-2686). This method not only permits the identification of known substances directly from the extracts, but also allows for the determination of absolute configuration of structures under suitable circumstance.
The development of tumors is a fundamental disease of higher organisms such as plants, animals and man. The generally recognized multi-step model of carcinosis assumes that due to the accumulation of several mutations in a single cell, the proliferation and differentiation behavior of the cell is changed to such an extent that, after benign intermediate stages, a malignant state with metastasis is attained.
The concept of cancer or tumor includes a syndrome with more than 200 different individual diseases. Tumor diseases can be benign or malignant. The tumors that cause the biggest impact are in the lung, the breast, the stomach, the cervix, the prostate, the head and the neck, the large intestine and rectum, the liver and the blood system. There are large differences with respect to the progression, prognosis and therapy amongst the individual diseases. More than 90 percent of the diagnosed cases relate to solid tumors which can be treated only with difficulty if at all, especially in advanced stages or when the tumor has progressed to metastasis.
The three pillars of combating cancer continue to be surgical removal, radiation and chemotherapy. To date, it has not been possible to develop pharmaceuticals which bring about unambiguous prolongations of survival times or a complete cure in the case of metastasizing solid tumors. It is therefore meaningful to discover new pharmaceuticals for fighting carcinosis.
A new way of treating cancer is the present of signal transduction from a cell surface receptor in the nucleus of the cell by inhibiting specific enzymes. The biological activity can be brought about by synthetic materials and also by natural products.
The search for new anti-infective agents is also meaningful since many diseases caused by infections are inadequately treated resulting in an increase in protozoic and fungal organisms which are resistant to pharmaceuticals commonly used at the present time.